Objective To evaluate the efficacy and safety of tripterygium for diabetic nephropathy. Methods All randomized or quasi-randomized controlled trials (RCTs or quasi-RCTs) of tripterygium for biabetic nephropathy were collected from The Cochrane Library (Issue 1, 2010), MEDLINE (1996 to March 2010), CNKI (1994 to March 2010), and CBM (1978 to March 2010). Two reviewers evaluated the quality of the trials and extracted the data independently. RevMan 5.0 software was used for meta-analyses. Results A total of 12 RCTs involving 862 patients were identified. The methodology of the included trials was poor and potential publication bias existed. The meta-analyses results showed: (1) Compared with the conventional treatment, the tripterygium showed more effects in reducing the 24-hour urinary protein (Clinical phase: WMD= –0.49, 95%CI –0.63 to –0.34, No phase: WMD= –0.60, 95%CI –0.96 to –0.24), and the urinary albumin excretion rate (UAER) (WMD= –148.75, 95%CI –238.01 to –59.48) was higher than that of the conventional treatment. (2) There were no significant differences between the two groups in the effect on the serum creatinine (Clinical phase: WMD= –8.43, 95%CI –18.15 to 1.29, No phase: WMD= –0.66, 95%CI –2.12 to 0.79) and creatinine clearance rate (WMD= 1.74, 95%CI –6.34 to 9.83). (3) Without enough data, it was uncertain to define the effect of tripterygium on lipids, blood pressure of the DN patients. (4) No severe adverse events or allergic reactions were reported. Conclusion Tripterygium may be a kind of medicine relatively safe and effective for diabetic nephropathy. However, the evidence is not b enough because of some low-quality trials and publication bias. Rigorously-designed, randomized, double-blind, and placebo-controlled trials of tripterygium for diabetic nephropathy are needed to further assess the effect.