The choice treatment for denture stomatitis are topical antifungals such as miconazole nitrate (MN). Targeting denture wearers, an experimental denture adhesive (EA) was developed containing polymeric microparticles (MPs) for the delivery of MN. Objectives: To investigate the systemic toxicity in rats of the EA added with MN MPs. Methods: Thirty-five Wistar rats received intraperitoneal injection of the materials: artificial saliva (AS) as solvent, Corega Cream® (CCDA), pure EA or EA added with MN MPs (sigla), and pure MN or MNMP. Animal behavior impairment (level 0-4) and weight (g) analyses were carried out at 0, 24, 48 and 72 h. Blood was collected to detect C-reactive protein. The intraperitoneal washing was analyzed through red blood cell and leukocyte counts and turbidity degree. Descriptive statistical analysis was performed for behavior and turbidity. Normality of red blood cells (thousand/L) and leukocytes (million/L) counts was verified (Shapiro-Wilk, p<0.0001). Statistical analysis was performed using Kruskall-Wallis and Mann-Whitney U tests with Bonferroni adjustment. Results: No significant difference between weights of groups was found for time (p=0,551). No behavior alterations level 2, 3 or 4 were observed. The C-Reactive protein was negative for all groups. The leukocyte and red blood cell counts showed significant difference between the groups AS and EA+MNMP (p=0.016 and p=0.009, respectively). No significant difference was found between EA+MNM and the CCA (p=0.917) group in the leukocyte count. Significance: The denture adhesive with antifungal presented similar results to those of the commercially available adhesive, and pure saliva was sufficient to cause peritoneum systemic toxicity