OBJECTIVE： To explore the clinical efficacy of methylprednisolone combined with tacrolimus in the treatment of elderly patients with primary nephrotic syndrome and their effects on natural killer （NK） cells， T lymphocyte subsets and histocompatibility complex （MHC）Ⅱ  level. METHODS： 88 elderly patients with primary nephrotic syndrome were selected and divided into single drug group and drug combination group， with 44 cases in each group. Single drug group was given Methylprednisolone tablet 0.8 mg/kg，qd （morning）， gradually decreasing to 4 mg/d. Drug combination group was additionally given Tacrolimus capsule 0.025 mg/kg，q12 h （1 h after meal）， adjusting drug dosage according to plasma concentration. Treatment course of 2 groups lasted for 6 months. Clinical efficacies of 2 groups were observed as well as 24 h urinary protein quantitation， serum albumin， renal function indexes （SCr， BUN）， TC， FIB， the number of NK， T lymphocytes subset （CD4+， CD8+， CD4+/CD8+）， MHCⅡ level before and after treatment. The occurrence of ADR was recorded. RESULTS： Total effective rate （72.73％） of drug combination group was significantly higher than that of single drug group （40.91％）， with statistical significance （P＝0.003）. Before treatment， there was no statistical significance in above indexes between 2 groups （P＞0.05）. After treatment， above indexes of 2 groups were improved significantly， and the improvement of 24 h urinary protein quantitation， serum albumin， SCr， BUN， FIB， NK cells， T lymphocytes subset and MHCⅡ level in drug combination group were significantly better than in single drug group， with statistical significance （P＜0.05）. The incidence of ADR in single drug group （6.82％） was slightly lower than in drug combination group （9.09％）， without statistical significance （P＝0.694）. CONCLUSIONS： Methylprednisolone combined with tacrolimus have significant therapeutic efficacy in the treatment of elderly primary nephrotic syndrome， can improve NK cells and T lymphocyte subsets level and decrease the expression of MHCⅡ with good safety.