In the present study, peri-implant tissue alteration was studied histologically, and then differences in the gene expression pattern of certain proteins were analyzed using cDNA microarray analysis, under the influence of static lateral load. Beagle dogs were divided into two groups: control and load. Three months after the extraction of mandibular premolars, two implants were placed in each side of the mandible. Each group was further divided into subgroups for loading times of 1, 7 and 14 days. Immediately after the implant installation, a loading device was adhered between the abutments of neighboring implants. Afterward, the expansion screw of the load group was activated by 360-degree rotation, resulting in 0.7 mm horizontal expansion. After sacrificing the dogs, peri-implant tissue was collected, then microarray analysis for the detection of gene expression was performed, as well as histology. Histology indicated that the peri-implant tissue broke down under the influence of the load. Microarray analysis demonstrated the presence of load-sensitive gene expression even after 1 day. Differences in gene expression patterns in concert with static lateral load were demonstrated, even at an early stage post-operation. Further study may help in the diagnosis of pathological overload.