It has been well established that droplets could be produced by various microchannels in many research and application areas. In this paper, we experimentally study the formation of droplets by flow focusing of two immiscible liquids in cross-flow microchannels. The used microchannels are featured by width of 100 µm and depth of 60 µm, which are fabricated with poly-dimethylsiloxane. The process of droplet formation is described in detail by changing the parameters which control the droplet size and generation rate. Different characteristic regimes are achieved over a large range of flow rates. We also numerically simulate the behaviors of droplets in the tested microfluidic device. The variation tendency of droplet formation frequency with different flow rates and transport properties of the continuous and dispersed phases are illustrated. The important parameters resulted from different flow conditions and configurations at the junctions and flow focusing section are also presented.