The present study was designed to assess the stress responses to a simulation model of the undersea environment that is similar to some undersea working conditions such as submarine rescue, underwater salvage and underwater construction. Restraint, hyperbaric air and immersion were chosen to produce the simulation stress model in rats for four hours. Rats were randomized into five groups: control group, restraint (R) group, hyperbaric air (H) group, restraint plus hyperbaric air (RH) group, and restraint plus hyperbaric air plus immersion (RHI) group. The results showed that the responses to the simulation stress model of the undersea environment induced by R, H, RH and RHI involved the upregulated norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) of the central nervous system (CNS), upregulated adrenocorticotropic hormone (ACTH), corticosterone (CORT) and blood glucose of the neuroendocrine system, upregulated interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) of the immune system, and increased anxiety in rats. Compared with hyperbaric air, restraint tended to activate stronger stress responses. Conclusively, this work established a simulation stress model of the undersea environment induced by restraint, hyperbaric air and immersion. It further provided experimental data of such a model that showed significant activation of the CNS, neuroendocrine and immune systems and anxiety in rats. In this experiment we provided an experimental basis for undersea work such as working aboard a submarine.