Polystyrene microplastics (MPs) have emerged as significant environmental contaminants, raising concerns about their potential deleterious effects on the skeletal system. Although osteocytes are the most abundant cell type in bone tissue, the impact of MPs on their function remains poorly understood. In this study, osteocytes were exposed to MPs with a diameter of 5 μm at a concentration of 100 μg/mL for 48 h. Our findings demonstrate that MPs can be internalized by osteocytes and induce cytotoxicity. Exposure to MPs induces oxidative stress via the accumulation of reactive oxygen species (ROS), subsequently precipitating cell cycle arrest and DNA damage. Moreover, MPs disrupted bone cell signaling and perturb the regulation of bone metabolism. Importantly, we found that MPs activated the cyclooxygenase-2 (COX2) signaling cascade, augmenting prostaglandin synthesis and consequently enhancing the secretion of pro-inflammatory cytokines. This cascade of events collectively contributes to osteocyte senescence. Notably, pharmacological inhibition of COX2 with aspirin significantly attenuates MPs-induced osteocyte senescence through suppression of prostaglandin biosynthesis. These findings suggest a potential link between MPs exposure and skeletal health at the cellular level. This study provides novel insights into the osteotoxicity of MPs.