Background The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.Methods Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21-47 years). The duration of hemodialysis was 3-12 months, with a mean duration of 11 months. For 4 patients, this was the second transplant; the previous graft survival time was 2-11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25-37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg·kg-1·d-1) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m2) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery. Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.Results No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post-surgery. Diagnosis of acute rejections was based on the clinical assessments and pathological biopsy results. According to the Banff 07 classification of renal allograft pathology, one of the patients was la and the other was I la; the C4d staining was negative in both patients. One patient received methylprednisolone plus cyclophosphamide and the other received antithymocyte globulin (ATG) therapy, both leading to successful reversion of the acute rejection. All patients were discharged postoperatively and all had normal renal function during the 7th to 12th month follow-up. Pulmonary infection occurred in 1 patient 4 months after surgery and was successfully cured. Conclusion Rituximab induction therapy can reduce the occurrence of postoperative humoral rejection in highly sensitized renal transplant recipients, suggesting that kidney transplantation may be safe and effective for these patients.