Abstract: Objective :To investigate the relationship between protein kinase C (PKC) and multidrug resistance (MDR) in KBY200 cells. Methods :PKC activity was assayed by the measurement of the incorporation of ³²P from γ-³²P ATP into peptide substrates. Western blotting was used for the assessment of PKC isoform expression. PKC activitor PMA were used to preincubate KBY200 cells to evaluate the importance of PKC in MDR. The cell inhibitory rate was evaluated by MTT. Results :The PKC activity of total and membrane fraction were higher in test group than those in control group, while PKC activity of cytosol fraction was lower. PKCα expression was upregulated in membrane fraction and downregulated in cytosol fraction in KBY200 cells after PMA preincubation. PKCβ expression was higher slightly in cytosol fraction but no alteration in membrane fraction in test group compared with control group. The values of IC₅₀ of YCR and ADR in test group were increased to 2275.5nmol/L and 233.25nmol/L respectively (p<0.01). Conclusion :PMA can increase the multidrug resistance of KBY200 cells, suggesting that PKC may be involved in the mechanism of multidrug resistance of tumor cells.