The authors hypothesized that FK506 improves maximal muscle force (PO) recovery during early muscle reinnervation. Rat peroneal nerve was unilaterally cut and repaired. Rats received subcutaneous injections of vehicle (controls) or FK-506 at 1 mg/kg (FK506-1MG) or 5 mg/kg (FK506-5MG) for 3 weeks. Extensor digitorum longus (EDL) isometric muscle P-0 was measured bilaterally 4 weeks postoperatively. FK506 treatment adversely affected body mass. With body mass as a covariate, the P-0 for denervated-reinnervated muscle in the FK506-5MG group was statistically significantly higher by 34 percent and 32 percent, compared with controls and FK506-1MG groups. There was no group difference for the contralateral, nerve-intact EDL muscle P-0, when loss of body mass was considered. NCAM immunohistologic data showed significantly better reinnervation of the denervated muscle in a dose-dependent fashion. Thus, FK506 treatment at high dose improves early recovery of force in denervated-reinnervated muscle, following nerve repair,when loss of body mass is considered.