Isocyanates are the raw materials that make up all polyurethane products. Isocyanate is a powerful irritant to the mucosal membrane of the respiratory tract, eyes and skin. Pulmonary symptoms, especially occupational asthma, are predominant manifestations of isocyanate toxicity. We report mental changes and compartment syndrome complicated with rhabdomyolysis as an extraordinary manifestation of acute isocyanate toxicity observed in a patient during the waterproofing of a water tank. A 58-year-old man recovered consciousness after six hours in the emergency department and complained of severe pain in the lower leg. The results of his laboratory test showed that his serum creatine kinase (15,250 IU/L) level had increased. The tissue pressure in both the lower legs had increased to 180 mmHg/170 mmHg (right/left). We performed fasciotomy on the second day of hospitalization. The patient was provided hyperbaric oxygen (HBO2) therapy of 2.0 ATA for 90 minutes twice a day for seven days. His condition gradually improved over five months, and he did not require amputation. He had a mild neurological disorder in his foot and was transferred to a rehabilitation center five months after hospitalization. It is important to note that when working with isocyanate, non-specific complications such as a change in consciousness as well as compartment syndrome with rhabdomyolysis can occur in a confined space or high-temperature environment. In addition, we found that compartment syndrome caused by isocyanate toxicity can be effectively treated with fasciotomy and HBO2 therapy.