We have developed a method to apply chemical therapeutic agents topically to the mouse maxillary tissue [24 (link), 78 (link)]. We used the maxillary topical application (MTA) model to apply oral microbial components [8 (link)]. The present study used the MTA model using 1 μg/ml unmethylated CpG oligonucleotide (CpG ODN: InvivoGen, San Diego, CA) or P. gingivalis lipopolysaccharide (LPS: InvivoGen). First, a custom-made oral appliance was fabricated using clear dental resin, covering the maxillary/palatal tissue between the molars. Mice were anesthetized and placed on a supine position. CpG ODN (3 μl) or LPS (3 μl) was pipetted over the maxillary tissue and the oral appliance was placed to hold the solution with a bite block for 1 hr in an anesthetization chamber. Mice were then transferred to the operation table and the oral appliance and bite block were removed. In general, there was no remaining solution in the mouth. Mice were returned to the cage in the vivarium. On Day 4 of the MTA, mice were euthanized by 100% CO2 inhalation and the maxillary tissue was harvested and fixed with 10% buffered formalin for histological evaluation.