We studied the influence of [DAla4]-dermorphin ([DAla4]-DM), its fragments ([DAla4]-DM2–7, [DAla4]-DM3–7, and [DAla4]-DM4–7) and analogs ([Trp1, DAla4]-DM, [DArg2, DAla4]-DM, and [DOrn2, DAla4]-DM) on the functional status of the thermoregulation system in rats at different thermal environments: cold (4–6°C), thermoneutral (27–28°C) and hot (31–32°C). [DAla4]-DM administration proved to induce temperature- and dose-dependent hypothermia and vasomotor responses. No activity of the peptide was observed in the hot environment. N-terminal shortening of the peptide inhibits its thermoregulatory activity. Tyr1 to Trp1 substitution nearly completely suppressed the thermoregulatory effects. DAla2 to DArg2 substitution decreased the hypothermic effect and only the vasodilatory response was observed in the comfortable environment. DAla2 to DOrn2 substitution completely suppressed the hypothermic effect in the cold environment and considerably attenuated the vasodilatory response in the thermoneutral environment.