Background: There is mounting evidence that moderate to high intensity exercise training has a key role in skeletal muscle adaption. Blood flow restriction (BFR) low intensity exercise training associated with unique effect on muscle hypertrophy. The purpose of the study was to investigate of effect of acute interval walking with blood flow restriction on phosphorylation of 4EBP1, P38, ERK and myostatin (MSTN) of skeletal muscle in inactive men., Methods: Five healthy inactive men were participated in 2 sessions with 14 days interspersed. Session one was including BFR by 5 intervals 3-min walking at 55%Maximum heart rate (MHR) and 1 min at rest. Session two was including 5 intervals 3-min walking at 55% MHRand 1 min at rest without BFR. All samples were collected at 30 min and 3 h after exercise test. Concentration of P38, ERK and MSTN skeletal muscle were evaluated by Western blotting. Dependent t-test and Independent t-test was used to analyze the data after subtracting the post-test score from the pre-test. However, there was a significant difference between the pre and post-test for 4EBP1 (P=0.001) and ERK (P=0.049) in the blood flow restriction group., Results: There was no significant difference between pre and post-test of P38 (P=0/452). Significant difference was observed for ERK (P=0.012) in acute interval walking (P=0.049). There was no significant difference between pre and post-test of 4EBP1 (P=0.064) and P38 (P=0/122). No significant difference was found between two group for concentration of 4EBP1 (P=0.068), P38 (P-0.091) and ERK (P=0.827), (P≥0.05)., Conclusions: This study has shown that acute interval walking with blood flow restriction does not activate MAPK pathway signaling in inactive men.