Objective To investigate the preventive and therapeutic effects and the mechanisms of pyrrol idine dithiocarbamate (PDTC) on the atrophy of denervated skeletal muscle. Methods Thirty adult Wistar rats of either gender, weighing (200 ± 10) g were randomly divided into 3 groups: group A (n=6, control group), group B (n=12, denervation group), and group C (n=12, PDTC treatment group). The sciatic nerves of the rats were only exposed without cutting off in group A, and the rats were made denervated gastrocnemius models in groups B and C. PDTC of 100 mg/(kg•d) was injected peritoneally in group C and an intraperitoneal injection of the same amount normal sal ine was given in group B. After 14 and 28 days, the gastrocnemius was harvested to measure the ratio of muscle wet weight; the levels of nuclear factor of κB (NF-κB)p65 protein and the opening of the mitochondrial permeabil ity transition pore (MPTP) in the gastrocnemius were detectedrespectively by Western blot and laser confocal scanning microscope; and the apoptotic cells in atrophic muscle were measured with TUNEL. Results The ratio of muscle wet weight in group A was 1.039 ± 0.115, and it significantly decreased in groups B and C (P lt; 0.05); after 14 and 28 days of operation, the ratio of muscle wet weight in group C significantly increased when compared with those in group B (P lt; 0.05). The expression of NF-κB p65 protein in group A was 0.224 ± 0.041; the expressions of NF-κB p65 in groups B and C significantly increased when compared with that in group A (P lt; 0.05); however, the expression of NF-κB p65 in group C was significantly lower than that in group B (P lt; 0.05). The MPTP fluorescence intensity in group A was 31.582 ± 1.754; the MPTP fluorescence intensity was significantly lower in groups B and C than in group A (P lt; 0.05), and the MPTP fluorescence intensity in group C was significantly higher than that in group B (P lt; 0.05). The rate of apoptosis in group A was 4.542% ± 0.722%; after 14 and 28 days of operation, the rates of apoptosis significantly increased when compared groups B and C with group A, and signiticantly decreased when compared group C with group B (P lt; 0.05). Conclusion PDTC can retard denervated skeletal muscle atrophy, and the effect may have a relationship with its inhibition on NF-κB, the opening of the MPTP, and the ratio of apoptosis.