Objective: To investigate the expression of CD2-associated protein(CD2AP) and α-actinin-4 in rats with adriamycin nephropathy, and to explore their possible effects on the development of proteinuria. Methods: Thirty SD rats, weighing from 140 to 160 g, were randomly divided into nephropathy model group and normal control group. The nephropathy model was established by a single intravenous injection of adriamycin(6 mg/kg). Normal control group received the same volume of 0.9% sodium chloride solution. At the end of the 2nd, 4th, 6th and 8th week after injection, the rats were sacrificed and their kidneys were acquired. The renal histology was observed by light microscope and electronic microscope. The semiquantitative western blot was used to detect the levels of CD2AP and α-actinin-4. Results: The protein levels of CD2AP in nephropathy model groups at the end of 2nd, 4th and 6th week were 3.0, 1.8 and 1.2 times of those in normal control group respectively. However, no appreciable alterations were observed in the expression level of α-actinin-4 at any time point. Conclusion: The expression of CD2AP is associated with the development of proteinuria in adriamycin nephropathy rats. But there is no relationship between the expression of α-actinin-4 and the increase of proteinuria.