Objective To investigate the application and significance of human leukocyte antigen(HLA) and cross-reactive antigen groups(CREGs) matching in highly sensitized recipients of renal allografts.Methods Recipient's panel reactive antibody(PRA)was detected by using complement dependent-micro lymphocytotoxicity test with lambda cell tray.Donor and recipient HLA classⅠtyping was performed with special monoclonal tray and HLA classⅡgene typing with microsequence specific primers(Micro-SSP). Fourteen highly sensitized patients with PRA positive(PRA40%)were observed in HLA CREGs matching and outcome of post-transplantation.Results Patients with 0,1,2 or 3 mismatching(MM) of HLA CREGs+DR were 4(28%), 6(44%)and 4(28%)cases respectively according to the the rule of CREGs matching and no case had 3~6 MM.However the cases of 0,1,2,3 and 4 MM were 1(7%),3(21%),5(36%)and 5(36%)respectively by the standard of conventional HLA antigen matching,without 4~6 MM and only 4 cases had shared 0~1MM.Only 9 patients were developed into acute rejection, and were reversed by OKT3 treatment after transplantation.Renal function was returned to normal in all patients.Conclusions Using CREGs matching criteria would significantly increase the chance of recipients to receive well-matched kidney and provide more chance for waiting recipients.Suitable HLA matching could play an important role in reducing the incidence of acute rejection and improving graft survival in sensitized patients.