Abstract: Objective To investigate the effects of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) on wound pathological characteristics, inflammatory responses, and cyclic adenosine monophosphate (cAMP)/transient receptor potential vanilloid subtype 1 (TRPV1) signaling pathways in a rat model of hemorrhoids. Methods Forty healthy male SD rats aged 6 weeks were randomly divided into control group, model group, NLRP3 agonist group, and NLRP3 inhibitor group, with 10 rats in each group. The control group received no intervention, while acute hemorrhoid models were established in the other three groups. After successful modeling, the NLRP3 agonist group and the NLRP3 inhibitor group were administered local subcutaneous injections of NLRP3 agonist and NLRP3 inhibitor at the wound site, respectively. The model group and the control group received subcutaneous injections of equal volume of saline. The pathological characteristics of the wounds in each group were observed and wound scores were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Western blot analysis was employed to detect protein expression levels of NLRP3, cAMP, and TRPV1 in the wound tissue. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect mRNA expression levels of NLRP3, cAMP, and TRPV1 in the wound tissue. Results Compared with the control group, the model group exhibited increased inflammatory cell infiltration, pronounced edema, disrupted tissue structure, and connective tissue hyperplasia in the wound tissue. When compared to the model group, the NLRP3 agonist group showed an increase in inflammatory cell infiltration, whereas the NLRP3 inhibitor group demonstrated a reduction in inflammatory cell infiltration. After intervention, compared with the control group, the model group had elevated wound scores and serum levels of TNF-α and IL-6. Additionally, the relative protein expression levels of NLRP3, cAMP, and TRPV1, as well as the mRNA expression levels of NLRP3, cAMP, and TRPV1 in the wound tissue, were increased in the model group (P<0.05). Following intervention, when compared to the model group, the NLRP3 agonist group showed an increase in all aforementioned indicators, whereas the NLRP3 inhibitor group exhibited a decrease in these indicators (P<0.05). Conclusion The NLRP3 inflammasome may participate in the development and progression of acute hemorrhoids in rats by activating the cAMP/TRPV1 signaling pathway.