Abstract: Objective 　To establish melphalan2resistant cell line of human multiple myeloma MOL P22/ R and to investigate it s biological characteristics and possible mechanisms of acquired resistance. Methods 　Melphalan2resistant cell line of multiple myeloma MOL P22/ R was established by continuous stepwise se2 lection in increasing concent ration of melphalan. Cell morphology, growth curve and population doubling time, protein level of P2gp, MRP and FANCD2 monoubiquitination were investigated to determine the biological features of MOL P22/ R cell line. The IC50 and resistance index ( R I) were measured by MTT assay. Results 　A melphalan2resistant cell line MOL P22/ R was successfully established . The resistance index ( R I) of MOL P22/ R cells was up to 6. 03. Besides melphalan it was cross resistant to many other chemotherapeutic agent s, such as ADM、CTX、DDP and VP216. Comparing with it s parent cell line, the multiplication time was postponed ( P < 0. 05), but the proportion of S phase wasn't significantly higher than parent cell line ( P > 0. 05) . Western blot studies showed that the levels of P2gp, MRP expression in the MOL P22/ R cells were similar with the sensitive cells, but enhanced FANCD2 protein monoubiquiti2 nation. Conclusion 　MOL P22/ R cell line with stable melphalan2resistance shows typical multidrug resist2 ance phenotypes and may serve as an ideal model for exploring the mechanism of MDR and the new route of reversing multidrug resistance. Over2expression of FANCD2 protein monoubiquitination might con2 t ribute to acquired drug resistance in MOL P22/ R.