OBJECTIVE: To explore a new approach for treatment of renal insufficiency with decorin (DCN) gene therapy. STUDY DESIGN: Male Sprague Dawley rats were subjected to 5/6 nephrectomy under aseptic conditions and randomly divided into sham-operated group (Group A), operation control group (untreated, Group B), blank control group (treated by empty vector-transfected fibroblast FB [LXSN], Group C), and treatment group (treated by FB [LDCNSN] cells, Group D). Changes in body weight, blood lipids, renal function, and renal tissues were observed. TGF-β1 and DCN expressions in renal tissues were detected with Western blot. RESULTS: Body weight and blood lipids were similar among the various groups 4 weeks after different treatments. The levels of BUN and Scr in Group D significantly declined as compared with those in Group C (p < 0.05). They moderately rose compared with basic values. DCN expression in renal tissues increased significantly in Group D after 4 weeks. There was no significant difference in TGF-β1 expression among Groups D, B, and C. Meanwhile, pathologically, damage to renal interstitium of rats in Group D mitigated significantly. The difference was significant as compared with Groups B and C. CONCLUSION: DCN is able to alleviate fibrosis and delay the progression of renal failure. © Science Printers and Publishers, Inc.