Chronic rhinosinusitis is a common disease difficult to cure. The role of combined intranasal antibiotic and mucolytic as an adjunct to oral antibiotic and decongestant treatment has not been evaluated. We performed a randomized, prospective, parallel study in 60 patients aged 12 years or older, recruited from the Ear, Nose and Throat (ENT) outpatient clinic at Siriraj Hospital, Bangkok, Thailand. All patients had chronic maxillary sinusitis documented by radiographs. They were randomized into 3 groups. One group was given standard treatment (STD) of amoxicillin 500 mg three times a day for 2 weeks and pesudoephedrine 60 mg three times a day for 4 weeks, one group was given intranasal thiamphenicol glycinate acetylcysteinate (TGA) plus STD, and the other group was given intranasal thiamphenicol glycinate acetylcysteinate (AC) plus STD. Intranasal medication was administered by nebulization once a day for 10 days at the clinic. After the treatment, clinical symptoms and signs decreased significantly in all treatment groups. The decrease in rhinorrhea and physical examination scores in the TGA group was statistically significant compared to the AC and STD groups (p < 0.05 both and p< 0.001 both, respectively). Compared to the baseline, maxillary sinus radiographs at 4 weeks after treatment initiation showed significant improvement in the TGA and AC groups (p <0.01 both). There was a significant regression of abnormal finding of X-ray in the TGA group (p <0.01 both).  The use of intranasal nebulized TGA as an adjunct to standard therapy of chronic rhinosinusitis improves symptoms and physical findings, and aids regression of radiographic abnormalities.