The purpose of setting up variable guidance lanes is to ease the traffic pressure on lanes with more traffic under the condition of ensuring the traffic capacity of the intersection. This study proposes a bi-level model-interactive relationship between variable guidance lane design and signal control and carry out a case study for a road in Wuhan, China. The design plan for the goal, combined with the design plan of the variable guidance lane, optimizes the signal timing plan of the intersection. A real case is modeled in VISSIM to simulate the design scheme of variable guidance lanes to verify the reliability and effectiveness of the bi-level model. The results showed that the average vehicle delay at the intersection was reduced by 20.65% after the bi-level model was optimized. The average error between model calculation results and simulation results is 9.88%. Moreover, the influencing factors of the proposed model are also carried out. The results show that when the traffic flow is greater than 1,000 pcu/h, the optimization effect of the model is more significant. When the traffic capacity gradually increases, the average vehicle delay calculated by the model is smaller. The design scheme and signal timing scheme proposed by the bi-level model can ensure the overall traffic efficiency of the intersection, improve the traffic efficiency of the traffic-stressed lanes, and further promote the space-time resource utilization of the intersection, optimize the space-time resources of the road network, and provide a scientific basis and new ideas and methods.