Abstract: Background and Objective: There is sufficient data that Chronic Unpredictable Stress (CUS) induced changes in nociception using different animal models. CUS is considered as a valuable animal model to study depression. Adenosinergic system plays a key role in pain transmission in different brain areas interacting with its receptors and other neurotransmitters. The effects of caffeine as a non selective adenosine receptor antagonist on the chronic unpredictable stress-induced changes in nociception using two experimental models of phasic and tonic pain was studied. Methods: CUS induced depressive-like condition; paw pressure test (phasic pain model) and writhing test (tonic pain model) were used. Methylxanthine caffeine was administered acutely (2, 20 and 40 mg kg-1) and long-term (8 mg kg-1 day kg-1, 4 weeks). Desipramine (10 mg kg-1 day-1, 4 weeks) was used as a reference antidepressant. Results: Single caffeine injection showed bidirectional effects, enhancing of CUS-induced antinociception in phasic model and abolishment of CUS-induced pro nociception in tonic model. Long-term caffeine administration per se increased nociception and similarly to the antidepressant desipramine was able to abolish the CUS-induced antinociception in paw pressure test in rats. Conclusion: The results underlined the different impact of mood depression on phasic and tonic acute pain and revealed the ability of caffeine to reverse CUS-induced changes in nociception depending on the duration of administration.