AIM: To investigate the effect of sitagliptin on the autopaghy and the expression of extracellular matrix in mesangial cells induced by advanced glycation end products (AGEs).METHODS: The cells were divided into 5 groups: control group, AGE group, and sitagliptin (5, 10 and 20 μmol/L) groups.After 48 h, the cell viability was measured by MTT assay, and the content of collagen (Col) Ⅳ in the supernatant of the cell culture was detected by ELISA.The protein levels of beclin-1, adenosine monophosphate-activated protein kinase (AMPK), p-AMPK, p70S6K and p-p70S6K were determined by Western blot.RESULTS: Compared with control group, the viability and the expression of Col IV induced by AGEs in the cultured mesangial cells were significantly increased (P<0.01).Sitagliptin decreased the viability and the expression of Col IV induced by AGEs in the mesangial cells in a dose-dependent manner.AGEs significantly inhibited the protein levels of beclin-1 and p-AMPK, but significantly increased the protein level of p-p70S6K.Compared with AGE group, sitagliptin significantly reversed the above results in a dose-dependent manner.CONCLUSION: Autophagy may mediate the protective effect of sitagliptin on mesangial cells induced by AGEs.