Objective To investigate the relationship between the nucleotide binding oligomerization domain like receptor protein 3 (NLRP3) inflammasome and inflammatory reaction of venous ulcer of lower extremity.Methods Twenty four patients with active venous ulcer of lower extremity (active ulcer group), 24 patients with non exudative venous ulcer of lower extremity as positive control (non-active ulcer group), and 24 patients with traumatic wound as negative control (traumatic-wound group) were enrolled. The clinical data of the three groups were compared, the tissue samples around the wound were harvested, and the expressions of NLRP3 protein were detected by immunohistochemistry in the three groups. Enzyme linked immunosorbent assay (ELISA) was used to detect the IL-1β and IL-18 protein levels, RT-PCR was used to detect the mRNA expression of apoptosis associated speck like protein containing CARD (ASC), caspase-1, c-Jun N-terminal kinase (JNK), p38, NF-κB p65 and NF-κB IkB-α, and Western blotting was performed to evaluate the level of NLRP3 inflammasome in wound tissues.Results The inflammatory response in the non-active ulcer group and trauma-wound group were milder than that in the active ulcer group. The level of IL-1β protein in the active ulcer group was higher than those in the non-active ulcer group and the traumatic-wound group ［ (146.6±11.6) pg/mL vs (80.9±14.2) pg/mL vs (85.0±19.5) pg/mL, F=136.200, P=0.000］. The results of RT-PCR showed that the mRNA relative expression of wound tissues in the active ulcer group of ASC ［ (0.03±0.012) pg/mL vs (0.021±0.005) pg/mL vs (0.016±0.004) pg/mL, F=18.106, P=0.000］, caspase-1 ［ (0.054±0.012) pg/mL vs (0.018±0.060) pg/mL vs (0.013±0.009) pg/mL, F=130.372, P=0.000］, NF-κB p65 ［ (0.093±0.015) pg/mL vs (0.043±0.014) pg/mL vs (0.038±0.013) pg/mL, F=110.950, P=0.000］ and JNK ［ (0.075±0.018) pg/mL vs (0.039±0.01) pg/mL vs (0.042±0.013) pg/mL, F=41.271, P=0.000］ were higher than those in the non-active ulcer group and the traumatic-wound group. And the mRNA relative expression of NF-κB IkB-α from the wound tissues in the active ulcer group was higher than that in the trauma-wound group ［ (0.085±0.015) pg/mL vs (0.041±0.016) pg/mL, P=0.000］. Western blotting showed that the level of NLRP3 protein from the wound tissues in the active ulcer group was higher than that in the non-active ulcer group (0.77±0.27 vs 0.60±0.21, P=0.042).Conclusion NLRP3 inflammasome is closely related to the wound in venous ulcer of lower extremity and provides a new target to the therapy of venous ulcer of lower extremity.