In order to accumulate experience in fault analysis and provide a reference for the establishment of operating mode, this paper describes and analyzes an actual incident of isolated operation of a regional power network. This incident originated from a 220 kV transmission line trip, which led to the isolated operation of the regional power grid, followed by load rejection, under-frequency load shedding, substation overvoltage, etc. This paper uses fault wave recording, simulation and theoretical analysis to explore the causes of the above acts such as load rejection, and discusses the measures to maintain the stable running of grid. Theoretical discussion and simulation results show that the proposed analysis is effective and correct. This work is supported by the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJ1704101).