A novel optofluidic refracrtive index (RI) sensor was proposed based on asymmetric Fraunhofer diffraction. In-plane optofluidic lens, light source, slit, diffraction pattern visualization zone and optical path were integrated into the microfluidic networks to avoid the manual alignment of the optical components as well as to reduce the cost of external bulky components. Unlike the conventional RI sensor, this device visualizes the bulk refractive index change of the liquid through a diffraction image, which is readily read-out for clinical diagnosis right at the point-of-care or on-site security check. In the experiment, the device can measure a RI change of as low as ~10-5 RIU. A low noise-equivalent detection limit (NEDL) of ~10-6 refractive index unit (RIU) and high sensitivity of ~1.1 × 104/RIU were achieved. The new device is practical and suitable to be extended for high throughput applications by simultaneously reading multiple chips with an 2D-array image sensor.