The tissue-type plasminigen activator (t-PA) is one of the important proteolysis factors in the pathogenesis of pulpal inflammation. The purpose of this study was investigate t-PA levels in clinically healthy and inflamed human pulp tissue specimens. Thirty-one pulpal tissue specimens (9 clinically healthy and 22 inflamed pulps) were obtained from extracted third molars. The levels of t-PA between clinically healthy pulp and inflamed pulp tissues were compared using casein zymography and an enzyme-linked immunosorbent assay (ELISA). The Wilcoxon-Mann-Whitney rank sum test was applied for the statistical analysis of the results. The main casein secreted by human pulp tissues migrated at 70 kDa and represented t-PA. Secretion of the t-PA protein was found to be higher in inflamed pulp when compared with clinically healthy pulp tissues (P<0.05). Similar results were also found by ELISA. Our findings demonstrated that t-PA levels and caseinolytic activities were significantly higher in inflamed pulp tissue compared with clinically healthy dental pulp. t-PA may play a key role in the breakdown of inflamed human dental pulp tissue.