BACKGROUND: Pillbugs have been proved to exert an effect on the proliferation and migration of vascular smooth muscle cells (VSMCs) through MTT assay and scratch assay, but the mechanisms are poorly understood. OBJECTIVE: To investigate the molecular mechanisms underlying pillbugs influencing osteopontin-induced VSMC migration and proliferation. METHODS: VSMCs from Sprague-Dawley rat thoraco-abdominal aorta were cultured in a common medium, and 3-5 generations of cells were selected. There were eight groups: control, osteopontin, pillbug water extract (0.5, 1.0, and 2.0 g/L) with osteopontin, and pillbug ethyl acetate extract (0.25, 0.5, and 1.0 g/L) with osteopontin groups. After 24 hours of culture, the expression levels of proliferating cell nuclear antigen (PCNA) and integrin kinase (ILK) were detected by western blot assay. RESULTS AND CONCLUSION: Pillbug water and ethyl acetate extracts both inhibited the expression of PCNA, especially when cultured in 0.5 g/L pillbug water extract (77.8% of the osteopontin group) and 1.0 g/L ethyl acetate extract (74.1% of the osteopontin group). 0.5 g/L pillbug water extract significantly downregulated ILK level induced by osteopontin, which was 81.4% of the osteopontin group, while pillbug ethyl acetate extract exposed no influence on ILK expression. These results reveal that pillbug water and ethyl acetate extracts both are able to inhibit osteopontin-induced VSMC proliferation, and the role of the pillbug water extract maybe associated with ILK protein pathway.