We have investigated the effects of cottonseed extract on the proliferation, differentiation and lipopolysaccharide (LPS)-induced production of local factors in murine clonal osteoblastic MC3T3-E1 cells. Ethanol extract of cotton seed (4~63 μg/mL) significantly increased the proliferatin of MC3T3-E1 cells (p <O.05). Moreover, cottonseed extract (10~50 μg/mL) caused a significant elevation of alkaline phosphatase (ALP) activity and collagen content in the cells. Lipopolysaccharide (LPS) is a potent stimulator of bone resorption in inflarnmatory diseases. We examined the effect of cottonseed extract on the LPS-induced production of tumor necrosis factor a (TNF-a) and nitric oxide (NO) in MC3T3-El cells. Treatment with cottonseed extract (10~50 μg/mL) decreased ilie 5 μg/mL LPS-induced production of TNF-α and NO in osteoblasts, suggesting that the antiresorptive action of cottonseed extract may be mediated by decrease in these local factors. This study suggests that cottenseed may contribute to antiresorptive action against osteoblastic cells, resulting in a beneficial effect in promoting the function of osteoblastic cells.