Abstract: Pterygium is a common ocular lesion whose exact etiology is a point of contention. Chronic inflammation and angiogenesis are two major proposed mechanisms of the disease in the current literature. The objective of this study is to examine these two mechanisms in a very well-designed setting. In a case-control study, 24 tissue specimens from the patients with primary moderate pterygium (cases) and 15 specimens excised from the nasal bulbar region in healthy counterparts (controls) were compared in terms of the count of mast cells (inflammation), as well as the status of Cd31/vascular Endothelial Growth Factor (VEGF) expression (angiogenesis) in Tabriz Nikookari and Sina Teaching Hospitals. The case (mean age: 58.08±10.03 years, 84% males) and control (Mean age: 62.33±9.19 years, 80% males) groups were age-and sex-matched (p = 0.19, 0.75, respectively). The mean mast cell count was significantly higher in the case group (27.72±15.19 vs. 12.00±7.09 cells mm-2, p = 0.001). The study of immunoreactivity revealed that the positive expression (moderate-severe) of CD31 was significantly more frequent in the case group (88 vs. 26.7%; p<0.001; Odds ratio = 20, 95% confidence interval 3.85-100). There was also higher rate of VEGF-positive (moderate-severe) cells in the group with pterygium (88 vs. 20%; p<0.001; Odds ratio = 33.3, 95% confidence interval 5.00-100). This study indicates that both inflammation and angiogenesis play pivotal role, in parallel, in pathogenesis of pterygium.