Vascular endothelial growth factor (VEGF) is a factor that induces angiogenesis and lymphangiogenesis and increases vascular permeability. VEGF is important in solid cancers for their growth, and its significance as a prognostic factor in cancer patients was also found in clinical studies. c-jun N-terminal kinase (JNK) plays a large role in the regulation of VEGF expression. A human oral squamous cell carcinoma cell line that constitutively expresses VEGF-A and VEGF-C was established. This cell line was treated with an inhibitor of JNK (SP600125), and the relationship between JNK and VEGF-A/VEGF-C expression was studied by real-time reverse transcription-polymerase chain reaction and Western blotting. We found that upon the addition of SP600125, the level of VEGF-A mRNA was elevated up through 12 h in comparison with that in the untreated group, but the level of VEGF-C mRNA was elevated only at 6 h. As to the effect of SP600125 on the protein levels of VEGF-A and VEGF-C, there were reduced levels of VEGF-A and VEGF-C at 3 h and increased levels of these proteins at 6 h. These results indicate that JNK plays a large role in regulating VEGF-A expression at the transcriptional level. As to VEGF-C expression, our results suggested that a molecule (s) other than JNK regulates VEGF-C expression. It was found that SP600125 did not affect the mRNA level and protein level of VEGF-A or VEGF-C in a similar manner, and the possibilities of posttranscriptional control of these proteins and increase in secretory capacity into the culture medium were considered. It is suggested that the levels of c-jun and p-c-jun affect the expression of VEGF-A and VEGF-C in vivo. The present results showed that JNK is involved in the regulation of VEGF-A and VEGF-C expression in oral squamous cell carcinomas.