Objective: To investigate the protective effects and potential mechanism of the compound 25-OH-PPD (PPD) on the glomerular mesangial cells (GMC) under high glucose condition. Methods: The hypertrophic GMC cells were established by DMEM containing glucose and randomly divided into five groups, including the normal control group (Control), the high glucose model group (HG, 25 mmol L-1), the PPD low dose group (1 mu mol L-1 PPD-L), the PPD middle dose group (5 mu mol L-1, PPD -M) and the PPD high dose group (10 mu mol L-1 UCN-H). The GMC were incubated for 48 h under different treatment factors. Total protein content was determined by Lowry method. The diameter of the single GMC and volume were measured by computer photograph analysis system. The GMC cell viability was analyzed by MTT assay. The level of malondialdehyde (MDA), the content of glutathione (GSH) and superoxide dismutase (SOD) activity were measured by ELISA. [Ca2+](i) transient was measured by Till image system and by cell-loading Fura-2/AM. The expression of COX-1 and COX-2 were also determined using ELISA method. Results: The viability of GMC and the total protein content were decreased in HG group, different dosage PPD group could increase these indexes (P<0.05). The level of MDA was increased, the content of GSH and SOD was decreased in HG group, while PPD could reduce the MDA and enhance GSH and SOD (P<0.05). Following treatment with different dosage (PPD-L, PPD-M or PPD-H), the [Ca2(+)](i) transient was reduced (P<0.05 or P<0.01). Moreover, the expression of COX-1 was decreased while COX-2 expression was increased in different dosage PPD groups. Conclusion: The protective effects of PPD on GMC from HG-induced hypertrophy may be associated with the inhibition of [Ca2+](i) transient and decreasing expression of COX-1 via the oxidative-stress injure pathway. (C) 2016 Elsevier B.V. All rights reserved.