Abstract: In order to study whether decline of glibenclamide（Gli）was changed in patients with diabetic nephropathy,pharmacokinetic and clinical studies of GLi were carried out in 12 cases of NIDDM（G.Ⅱ）whose renal function tests were abnormal with proteinuria,decreased Ccr and increased BUN and in 4 NIDDM（G.Ⅰ）without any renal function disorders.The results disclosed that the mean value of rate constant of decline（β）in G.Ⅱ was significantly less than that in G.Ⅰ（P＜ 0.01）,T1/2 was 5.4hr in G.Ⅰ but 17.8hr in G.Ⅱ.According to regression calculation,the change in β value correlated significantly with the ratio of Ccr/BUN（r=0.59,p＜0.02）.This means that the elimination of Gli was slower in NIDDN patients with impaired renal function.After Gli therapy,the Gli concentration at the 24th hr in the 1st,2nd and 3rd week in G.Ⅱ were significantly higher than that of G.Ⅰ（P＜0.05）.It is evident that Gli was accumulated in patients with diabetic nephropathy.