AIM：To investigate cell apoptosis in diabetic foot ulcers and the effect of  advanced  glycosylation end  products (AGEs) on apoptosis in human fibroblast cells. METHODS：Diabetic foot patients (n=18) and 18 age-matched non-diabetic controls were recruited. The clinical and biochemical features were compared by statistics methods. Skin biopsies were obtained from foot. Cleaved caspase-3 was measured by immunohistochemistry using the technique of streptavidin-biotin complex (SABC) staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique was used to detect apoptosis of the skin tissues. Human primary foreskin fibroblasts were isolated and cultured in the presence of 5.6 mmo/L glucose, 25 mmo/L glucose, fluctuant glucose (changing the glucose from 5.6 mmo/L to 25 mmo/L every 8 h) or AGEs (150 mg/L, containing 5.6 mmo/L glucose). After 72 h treatment, Western blotting was used to determine the levels of the apoptotic protein cleaved-caspase-3. Other cells were trypsinized, washed with cold PBS and incubated with PI and Annexin V-FITC, then analyzed by flow cytometry to detect cell apoptosis. RESULTS：Diabetic patients had higher levels of fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycosylated hemoglobin A1c (HbA1c), and longer wound duration. The protein level of cleaved caspase-3 was significantly higher in diabetic group, suggesting that apoptosis was increased in diabetic skin tissues. TUNEL analysis showed that apoptotic index was higher in diabetic group compared with that in non-diabetic group (8.4%±1.5% vs 3.8%±08%), which further confirmed that cell apoptosis was increased in diabetic foot tissues. In human fibroblasts, the levels of cleaved caspase-3 in normal group, sustained high glucose group, fluctuant high glucose group and AGEs group were 080±0.13, 1.22±0.18, 1.46±0.32 and 1.83±0.25, respectively. The apoptotic rates detected by flow cytometry were 2.43%±0.19%, 2.89%±0.51%, 3.99%±0.24% and 6.83%±0.36%, respectively. Both the level of cleaved caspase-3 and the apoptotic rate in AGEs group were higher than those in normal glucose group and sustained high glucose group. CONCLUSION：Increased apoptosis in diabetic foot ulcers is one of the most important reasons for impaired wound healing. As compared to sustained high glucose and glucose fluctuations, AGEs induce greater apoptosis in human fibroblast cells.