Objective:To investigate the regulatory effects of Yiqi Huoxue Huashi formula and its decomposed recipes on the podocyte slit membrane protein α-actinin-4 and CD2AP in rats with passive Heymann nephritis (PHN). MethodsMale Wistar rats were used to establish the classical PHN model. The successful modeling rats were randomly assigned into model group, cyclosporine group, Yiqi Huoxue Huashi formula group, Yiqi recipe group, Huoxue recipe group and Huashi recipe group. The normal rats were used as controls. The drug treatment groups were treated with the corresponding drug by intragastric administration, and the control and model groups were treated with equal volume of 0.9% NaCl solution. The treatment course was 6 weeks. Blood was drawn from the orbital venous plexus of rats at weeks 0,2, 4 and 6, and 24-hour urine was collected using metabolic cages. The serum levels of albumin (Alb), creatinine (SCr) and urea nitrogen (BUN), and the 24-hour urinary protein quantification (UPRO) were measured by automatic biochemical analyzer. After intervention, the kidneys were collected. The morphological changes of kidney tissues were observed under the light microscope after HE staining, and the morphological changes of glomerular basement membrane, podocytes and podocytic process were observed under the transmission electron microscope. The mRNA and protein expression levels of α-actinin-4 and CD2AP in kidney tissues were detected by PCR and Western blot.  Results:①Compared with the control group, the levels of UPRO and SCR increased significantly (P<0.05) and the level of Alb decreased significantly (P<0.05) in the model group at each time point. Compared with the model group, the level of UPRO decreased significantly at weeks 4 and 6 (P<0.05), and the level of Alb decreased significantly at weeks 2,4 and 6 (P<0.05), while the levels of SCr and BUN increased significantly at weeks 2,4 and 6 (P<0.05) in the cyclosporine group. Compared with the model group, the level of UPRO decreased significantly in the Yiqi Huoxue Huashi formula group only at week 6 (P<0.05). Compared with the cyclosporine group, the levels of SCr and BUN decreased significantly in the Yiqi Huoxue Huashi formula group at weeks 2,4 and 6. ②Compared with the control group, results observed under the light microscope showed in the model group, the glomerulus was obviously enlarged, the basement membrane was diffusely thickened, the capillary loops were compressed and some renal tubular epithelial cells were swollen; under the electron microscope, it was revealed in the model group that there were a large number of electron dense deposits under the epithelium and the podocytic process were widely fused or disappeared. Compared with the model group, the glomerular lesions in all drug treatment groups were alleviated. ③Compared with the control group, the mRNA and protein expression levels of α-actinin-4 increased significantly (P<0.05), while those of CD2AP decreased significantly (P<0.05) in the model group. Compared with the model group, the mRNA and protein expression levels of α-actinin-4 were down-regulated significantly (P<0.05), while those of CD2AP were up-regulated significantly (P<0.05) in the cyclosporine group. Compared with the model group, the protein expression level of α-actinin-4 was down-regulated significantly in the Yiqi Huoxue Huashi formula group (P<0.05). ④Compared with the model group, the levels of UPRO, Alb, SCr and BUN showed no obvious changes in all of the decomposed recipe groups at each time point (P>0.05). Pathological observation showed that glomerular injury was obviously relieved in all of the decomposed recipe groups compared with the model group. Compared with the model group, the mRNA and protein expression levels of α-actinin-4 were down-regulated significantly in the Yiqi recipe group (P<0.05), while those of CD2AP were up-regulated significantly in the Huoxue recipe group (P<0.05).  Conclusion:Yiqi Huoxue Huashi formula significantly reduces the urinary protein level and alleviates glomerular injury in PHN model rats, and the mechanism may be related to down-regulation of α-actinin-4 expression and up-regulation of CD2AP expression. Moreover, among its decomposed recipes, Yiqi recipe can inhibit α-actinin-4 expression and Huoxue recipe can promote CD2AP expression.