Introduction: Association between single-nucleotide polymorphisms (SNPs) in mu OPIOID receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and OPIOID addiction.Methods: 79 OPIOID-dependent subjects (55 males, 24 females) and 134 non-addict or control individuals (74 males, 60 females) participated in the study. Genomic DNA was extracted from volunteers’ peripheral blood and exon 3 of the mu OPIOID receptor gene was amplified by polymerase chain reaction (PCR) whose products were then sequenced.Results: Three different heterozygote polymorphisms were observed in 3 male individuals: 759T>C and 877G>A mutations were found in 2 control volunteers and 1043G>C substitution was observed in an OPIOID-addicted subject. Association between genotype and OPIOID addiction for each mutation was not statistically significant.Discussion: It seems that the sample size used in our study is not enough to confirm or reject any association between 759T>C, 877G>A and 1043G>C substitutions in exon 3 of the mu OPIOID receptor gene and OPIOID addiction susceptibility in Iranian population.