Objective To observe C4d deposition in renal allografts of rats undergoing chronic allograft nephropathy (CAN), and to analyze the effects of immunosuppressants on deposition of C4d in peritubular capillaries. Methods The renal grafts of Fisher 344 rats were orthotopically transplanted into Lewis rats to create CAN models, and all the recipients were given cyclosporine A (CsA) 10 mg/(kg· d)×10 d after operation. The models were then divided into 5 groups (each n=9): Group A was normal saline control group, only receiving vehicle orally; Group B, C, D, and E received CsA 6 mg/(kg·d), RAPA 0.8 mg/(kg·d),FK506 0.15 mg/(kg·d),and MMF 20 mg/(kg· d), respectively. The renal allografts were harvested after three rats were sacrificed at the 4^th, 8^th and 12^th weeks post-transplantation. The histological changes were assessed according to Banff 97 standard. The deposition of C4d was detected by immunofluorescence method. Results C4d deposition in peritubular capillary(PTC) was found in all the allografts at the 4^th week after transplantation, while there were no obvious clinical pathological changes of CAN in all groups, and the Banff scores were not significantly different among different groups (P>0.05). CAN manifestations of different degrees were observed 8 weeks after operation, with increased C4d deposition in the PTC. Severest CAN was observed at the 12^th week after operation, accompanied by the most C4d deposition in the PTC. C4d deposition was positively correlated with the severity of CAN (r=0.894, P=0.000). Compared with the control group, CsA and FK506 showed no significant effect on C4d deposition (P>0.05); however, MMF and RAPA significantly decreased C4d deposition (P<0.05). Conclusion Deposition of C4d in PTC may appear in allografts earlier than the pathological changes of CAN, and the deposition is associated with the progression of CAN. MMF and RAPA can inhibit the progression of CAN, while CsA and FK506 can not.