Trilayered polypyrrole (PPy) actuators have high stress density, low modulus and have wide potential biological applications including use in artificial muscles and in limb prosthesis after limb amputation. This article examines the in vivo biocompatibility of actuators in muscle using rabbit models. The actuators were specially designed with pores to encourage tissue in growth; this study also assessed the effect of such pores on the stability of the actuators in vivo. Trilayered PPy actuators were either laser cut with 150 µm pores or left pore-less and implanted into rabbit muscle for 3 days, 2 weeks, 4 weeks and 8 weeks and retrieved subsequently for histological analysis. In a second set of experiments, the cut edges of pores in porous actuator strips were further sealed by PPy after laser cutting to further improve its stability in vivo. Porous actuators with and without PPy sealing of pore edges were implanted intramuscularly for 4 and 8 weeks and assessed with histology. Pore-less actuators incited a mild inflammatory response, becoming progressively walled off by a thin layer of fibrous tissue. Porous actuators showed increased PPy fragmentation and delamination with associated greater foreign body response compared to pore-less actuators. The PPy fragmentation was minimized when the pore edges were sealed off by PPy after laser cutting showing less PPy debris. Laser cutting of the actuators with pores destabilizes the PPy. This can be overcome by sealing the cut edges of the pores with PPy after laser. The findings in this article have implications in future design and manufacturing of PPy actuator for use in vivo.