An RF-powered wireless three-channel implantable bio-sensing microsystem is developed with blood pressure, EKG, and core body temperature sensing capability for untethered genetically engineered laboratory mice real-time monitoring. A flat silicone blood pressure sensing cuff with a MEMS capacitive pressure sensor is employed to form a novel less-invasive blood pressure sensor, which avoids vessel occlusion, bleeding, and blood clotting associated with the conventional catheter-based sensors. The implantable microsystem can be powered by an adaptively controlled external RF energy source at 4 MHz to ensure a stable on-chip power supply. The overall system dissipates 200 μW and achieves a blood pressure sensing resolution of 1 mmHg within 1 kHz bandwidth, an EKG sensing resolution of 7.4 bits, and a temperature sensitivity of 19 mV/°C measured from 22 °C to 43 °C. A prototype packaged sensor exhibits a weight of 495 mg, which is approximately 2% of a laboratory mouse body mass. On-going research effort is devoted to demonstrate in vivo performance in laboratory animals.