Infectious sinusitis, a common condition seen in adult pheasants, is primarily caused by Mycoplasma gallisepticum. The aims of the present study were to investigate the pathogenicity of M. gallisepticum in 14-day-old pheasants and evaluate the macrolide antibiotic tylvalosin (TVN) as a treatment for infectious sinusitis. The minimum inhibitory concentration of TVN for five isolates of M. gallisepticum taken from pheasants confirmed their susceptibility to TVN (range: 0.002 to 0.008 µg/ml). One of the isolates (G87/02) was inoculated intranasally into 72 pheasants (two groups of 36) at 14 days of age. Eight days later, when 18/72 (25%) of the pheasants showed clinical signs, one group was treated with 25 mg TVN/kg bodyweight daily in drinking water for three consecutive days. An uninfected, unmedicated control group (n=12) was also included. In contrast to the uninfected control group, a range of clinical signs typical of infectious sinusitis with varying severity was observed in challenged birds and M. gallisepticum was re-isolated from the infraorbital sinus and the eye/conjunctiva at necropsy, 22 days post challenge. In comparison with untreated birds, medication with TVN significantly reduced clinical signs and the re-isolation/detection of M. gallisepticum (P≤0.0021). The daily liveweight gain of treated birds was significantly increased in comparison with untreated birds (P=0.0002), and similar to daily liveweight gains observed in the uninfected control group. In conclusion, TVN at 25 mg/kg bodyweight daily for three consecutive days in drinking water was efficacious in the treatment of M. gallisepticum infection induced by challenging 14-day-old pheasants.