Objective: To evaluate the antinociceptive and anti-inflammatory activities and the toxic effects of Rhipicephalus microplus saliva for elucidating the modulation mechanism between arthropod saliva and host. Methods: For saliva collection, engorged ticks were obtained from a controlled bovine infestation and collected by natural fall. The ticks were fixed and injected pilocarpine 0.2％for induction of salivation. Saliva was collected, lyophilized and stored at - 80 ℃. Cytotoxic activity was assessed by the hemolysis method (25, 50, 100, 200 and 300 μg/mL) and MTT cell viability assay (2.5, 5, 10, 20 and 40 μg/mL) for 24, 48 and 72 h. Anti-inflammatory activity was evaluated using the method of neutrophil migration to the peritoneal cavity of mice at doses of 10, 15 and 20 mg/kg; antinociceptive activity was assessed using the acetic acid-inducedwrithing test, and formalin-induced paw-licking in mice at dose of 15 mg/kg. Results: Saliva did not cause erythrocytes hemolysis at any concentration tested, as well as did not decrease cell viability in the MTT assay. Saliva inhibited neutrophil migration by 87％ and 73％ at doses of 15 and 20 mg/kg, respectively. In the nociceptive tests, saliva presented analgesic activity of 69.96％ in the abdominal writhing test, and of 84.41％ in the formalin test. Conclusions: The study proves that Rhipicephalus microplus saliva has significant in vivo anti-inflammatory and antinociceptive activities. The data presented herein support the development of further studies to elucidate the active principles of Rhipicephalus microplus saliva and its mechanism of action and,in future, to develop novel anti-inflammatory and analgesic drugs.