OBJECTIVE: Current diagnostic methods of inflammatory periodontal diseases, e.g., visual evaluation, periodontal probing, and radiographs, are either subjective or insensitive. Intra-oral high-frequency ultrasound was investigated to quantify inflammation by detecting tissue dimensional and perfusion changes. METHODS: A cohort of 15-month-old mini-pigs, 4 female/male each, was analyzed. Pre-molars (PM) 3 and 4, as well as first molars (M1), were scanned. In bi-weekly time intervals all 4 quadrants were randomly enrolled and bacterial injection followed each quadrant scan in a weekly fashion. Soft tissue dimensions were obtained from B-mode images and statistically analyzed to identify correlations to inoculation time, i.e., response to bacterial loading, tooth type and sex, using analysis of variance and regression analysis. Color flow velocity and power-weighted color pixel density was obtained and statistically analyzed analogous to soft tissue. RESULTS: Soft tissue thickness increased significantly post-inoculation at 1 and 2 mm below the free gingival margin for both genders and all observed teeth. The significance lasted for weeks 2, 4 and 6, except for female M1s (4 weeks). Color flow velocity was significantly higher compared with baseline for 6 weeks, except for male PM4 (2 weeks). Color flow power did not show significance for PM3 and 4, only in M1 (except male week 4). Significance also extended to tooth type and sex. CONCLUSION: Periodontal tissue dimension and color flow velocity increased in correlation to bacterial inoculation. Further studies are needed to obtain an understanding of the underlying biology observed here. Eruption of dentition may have been a confounding factor for inflammation interpretation.