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Background: Metalloproteinase-9 exists in the basement membrane of normal tissues and is a major factor in cancer invasion and lymphatic metastasis. Smoking has been reported to increase the metalloproteinase level, but the role of opium consumption in metalloproteinase level has not yet been examined. The current research intended to examine the impacts of opium consumption on the serum levels of metalloproteinase. Methods: This case-control research was conducted in Kerman (in the southeast of Iran), after getting medical approve by the ethics committee. Case group of 33 non-smokers with no active inflammatory diseases who had the experience of inhaled opium and its derivatives were compared with a control group of 40 non-smokers with no active inflammatory disease and no experience of inhaled opium and its derivatives. Student's t-test, mean, and chi-square test were employed to determine the correlation between the variables. Findings: No statistically meaningful variation was detected in plasma metalloproteinase concentration between the case and control groups (P = 0.160). Also, there was no significant relation between the plasma metalloproteinase concentration and urinary morphine in case groups (P = 0.410), but a statistically significant correlation was found between gender and metalloproteinase in both the case and control groups (P = 0.003). Conclusion: According to the possible role of opioid drugs directly on cancer and the prognosis metalloproteinase and cancer, further studies are suggested. [ABSTRACT FROM AUTHOR]