Although mechanical stress has been shown to regulate bone modeling and remodeling, the mechanisms of bone remodeling after mechanical stress loading are not fully understood. In this study we determined the effects of cyclic mechanical stretch of varying magnitudes and durations on the activation of JNK and p38 in MC3T3-E1 cells. Phosphorylation of both JNK and p38 was observed 5 min after the onset of stretch-load and increased proportionally with elongation. However, a marked increase in the phosphorylation of p38 but not JNK was observed when cells were stretched to 4% elongation. These observations raise the possibility that JNK and p38 play different roles in bone remodeling depending on the magnitude and duration of mechanical stretch.