Background <p>To investigate Quorum-Sensing inhibition by furanone compounds in Pseudomonas aeruginosa keratitis rabbit model.</p> Methods <p>Thirty adult New Zealand White rabbits were used. Anesthetized rabbits were intrastromally injected with Pseudomonas aeruginosa (P. aeruginosa). The rabbits were divided into six groups: the control group (infected only with P. aeruginosa), group A (50 mg/mL ceftazidime), group B (0.1 mg/mL furanone), group C (0.2 mg/mL furanone), group D (0.3 mg/mL furanone), and group E (20% dimethyl sulfoxide). One drop of the treatment was applied every hour for 3 days, starting 1-h post-inoculation. Rabbits were then sacrificed, and corneas were analysed clinically, microbiologically, histologically, and biochemically. One-way analysis of variance was used for the mean comparison of independent groups. The Least Significant Difference method was used as a post-hoc test for pairwise comparisons.</p> Results <p>In all evaluations, the antibiotic group (group A) showed the best therapeutic response. The slit-lamp examination score of group C was significantly lowered than those compared of to the control (<i>p</i> = 0.009) and E groups (<i>p </i>= 0.014). Histological evaluation showed that inflammation is decreased in groups B, C, and D. Levels of cyclooxygenase-2 (COX-2), superoxide dismutase-1, and reactive oxygen species (ROS) were lowest in the antibiotic-treated group, whereas the highest levels were detected in the control group. Notably, the COX-2 levels in group B and ROS levels in groups B and C were significantly lower than in control group. (<i>p</i> = 0.045, <i>p</i> = 0.039 and <i>p</i> = 0.045, respectively).</p> Conclusion <p>Furanone compounds may have minimal therapeutic effects against Pseudomonas keratitis. Its therapeutic effect has not been observed to be sufficient compared with that of antibiotics. Further studies are needed to investigate their protective effects and mechanisms.</p>