To investigate the role of miR-200c-3p in osteoarthritis (OA) and explore its downstream molecular mechanism. Methods OA animal model was established through destabilizing the medial meniscus. OA cell model was established through treating primary mouse chondrocytes with LPS. RT-qPCR was used to measure the expression level of miR-200c-3p in OA animal model and control animal model. The expression levels of miR-200c-3p and Zeb1 in primary mouse chondrocytes treated with or without LPS were detected by RT-qPCR. CCK-8 assay was applied to measure the proliferation of OA cells with miR-200c-3p overexpression. Flow cytometry was performed to analyze the apoptotic rate of OA cells after miR-200c-3p was overexpressed. ELISA assay was conducted to examine the concentration of inflammatory factors (IL-1β, IL-6, TNF-α) in OA cells with miR-200c-3p overexpression. Bioinformatics analysis, RNA pull down and luciferase reporter assay were conducted to demonstrate the interaction between miR-200c-3p and its downstream target. Functional rescue assays were used to verify the effect of Zeb1 on the functional role of miR-200c-3p. Results MiR-200c-3p was significantly down-regulated in OA mice articular cartilage tissues and lipopolysaccharide (LPS)-treated primary mouse chondrocytes. Zeb1 was up-regulated in LPS-treated primary mouse chondrocytes. Upregulation of miR-200c-3p significantly inhibited lipopolysaccharide induced chondrocyte apoptosis and inflammatory injury. Zeb1 is the downstream target of miR-200c-3p. Zeb1 overexpression reversed the effect of miR-200c-3p overexpression on chondrocyte apoptosis and inflammation in an OA mouse model. Conclusion MiR-200c-3p suppresses chondrocyte apoptosis and attenuates inflammation in OA mouse model by targeting Zeb1, which contributes to finds effective therapeutic target for OA.