Walking combined with blood flow reduction (BFR‐walk) elicits muscle hypertrophy. However, the skeletal muscle intracellular signalling behind this response is currently unknown. Aim To investigate the effects of BFR‐walk on mechanistic target of rapamycin (mTOR) and mitogen‐activated protein kinase (MAPK) signalling pathways in young men. Methods Six young men performed 20 min of treadmill walking at 55% of their predetermined maximum oxygen uptake. A pressure cuff belt was applied to the most proximal thigh of only one leg (BFR‐Leg, external compression was 240 mmHg), whereas the other leg (CON‐Leg) was without BFR during walking. Muscle biopsies were taken from the vastus lateralis of the CON‐Leg before exercise and in both legs 3 h after exercise. Results Erk1/2 phosphorylation levels were significantly (P < 0.05) increased after exercise in both legs; however, only the BFR‐Leg saw an increased phosphorylation of p38. For mTOR signalling, there were no changes in Akt, mTOR or S6K1 phosphorylation levels before or after walking. However, eEF2 phosphorylation level was significantly (P < 0.05) lower for the BFR‐Leg 3 h after walking compared with CON‐Leg. Conclusion BFR‐walk exercise may activate some intracellular signalling cascades that are associated with muscle hypertrophy in young men.