The dysregulated circular RNAs (circRNAs) are relevant to the development of osteoarthritis (OA). The circRNA serpin family E member 2 (circSERPINE2) is dysregulated in OA, while the role and mechanism of circSERPINE2 in OA are largely unknown. The aim of our research is to explore how and whether circSERPINE2 regulates interleukin-1β (IL-1β)-caused chondrocyte damage in OA. In the present study, the chondrocytes (CHON-001 cells) were exposed to IL-1β to mimic the injury in OA. CircSERPINE2, microRNA-495 (miR-495) and transforming growth factor-β receptor 2 (TGFBR2) abundances were detected via quantitative reverse-transcription polymerase chain reaction (qRT-PCR) or Western blot. Cell apoptosis was assessed via viability, apoptotic rate and caspase-3 activity. Extracellular matrix was investigated by levels of Sry-type high-mobility-group box 9 (SOX9), collagen type II α 1 (COL2A1) and Aggrecan using Western blot. The interaction among circSERPINE2, miR-495 and TGFBR2 was assessed via dual-luciferase reporter analysis and RNA immunoprecipitation (RIP). The results showed that circSERPINE2 expression was reduced in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 overexpression mitigated IL-1β-caused apoptosis and extracellular matrix degradation. miR-495 was targeted by circSERPINE2 and up-regulated in OA patients and IL-1β-treated chondrocytes. miR-495 up-regulation reversed overexpression of circSERPINE2-mediated inhibition of apoptosis and extracellular matrix degradation. TGFBR2 was targeted by miR-495 and lowly expressed in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 could mediate TGFBR2 expression by binding with miR-495. As a conclusion, circSERPINE2 attenuated IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis, indicating a new target for OA treatment.