In this paper we investigated the effect of ultrasonic insertion of neural probes on tissue induced immune response. We report reduction of the activated microglia population by a factor of 1.96, measured over 18 insertions. This suggests decreased immune response for neural probes inserted using ultrasonic insertion. This addresses a key requirement of increasing the operational lifetime of neural probe recording sites. A wirelessly connected neural probe system is used for in vivo electrical, mechanical, and ultrasonic response measurement. A chronic mouse model with in vivo two-photon excited fluorescence microscopy combined with the neural interface is developed to investigate the immune response of the brain, as a potential cause for microelectrode failure with continuous electrical neural measurements.