Hypertrophic scar (HS) remains a major problem in plastic surgery. In order to explore the regulative effect of phosphatase and tensin homolog (PTEN) on HS, PTEN and AKT expression was detected by reverse transcription PCR, immunohistochemistry and western blot. Adenovirus-mediated PTEN overexpression in cultured hypertrophic scar fibroblasts (HSFBs) and normal skin fibroblasts was also introduced to evaluate its biological function. Our results showed that PTEN expression was significantly decreased in HS whereas p-Akt level was significantly higher in HS compared with normal skin (P < 0.01). Furthermore, we found that adenovirus-mediated PTEN overexpression led to decreased AKT activation, and significantly reduced cell proliferation and collagen synthesis of HSFBs, while increased the apoptosis. Taken together, these data suggest that PTEN inhibits proliferation and function of HSFBs through AKT pathway. Our results reveal a novel biological role for PTEN/AKT pathway in HS and suggest PTEN as a potential therapeutic target for HS treatment.