The objectives of this study were to characterize the inflammatory response after microchip insertion, evaluate pain response and swelling at the microchip insertion site, and measure migration of the microchips. Eighteen mature Quarter Horse mares were separated by expected parturition dates and then assigned randomly to treatment groups. The microchip group (n = 7) had microchips inserted using a sterile needle and syringe; the sham group (n = 7) had a needle inserted but no microchip; and the control group (n = 4) had no insertion. The inflammatory response was measured over a 2-week period by measuring dermal temperature, response to pressure, and swelling at the insertion site and plasma serum amyloid A (SAA). For the migration component of the study, radiographs of the seven microchipped horses were taken over 6 months after insertion. These radiographs allowed measurement between a select vertebral point and the microchip. The microchip and sham insertion did not cause a detectable increase in temperature. Algometer readings, used to quantify pressure necessary to induce a pain threshold response, indicated that microchip insertion area was more sensitive than sham insertion at 2 hours, day 1, and day 3 post insertion. Visible swelling began 2 hours postinsertion and resolved by day 3. SAA concentrations were affected by day following insertion, but not by treatment group. Increases in SAA concentration could not be matched with local insertion reactions. Migration was not detected in any of the horses during the 6 months within a 0.7-cm margin of error.