Objective To evaluate the effectiveness and safety of spironolactone for diabetic nephropathy. Methods We electronically searched CENTRAL (issue 3, 2008), MEDLINE (1950 to August 2008), EMbase (1984 to August 2008), CNKI (1994 to September 2008), and VIP (1989 to August 2008). We also checked the reference lists of all papers identified for further trials. Randomized controlled trials (RCTs) and quasi-RCTs were identified and analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions. Results Three RCTs were included. Meta-analysis was not performed due to heterogeneity. Trials showed that spironolactone might decrease urinary albumin excretion, but could scarcely play an important role on kidney function and blood pressure. Conclusion Affirmative assessment cannot be made about the effectiveness and safety of spironolactone for diabetic nephropathy according to the limited existing trials. Large-scale, high-quality RCTs are needed to confirm or refuse the available evidence.