This study aimed to investigate the effect of quercetin without intranasal inflammation and oxidative stress in nasal and sinus mucosa, but also in serum, lungs and brain in a rat model of acute nasal and sinus inflammation induced by administration of lipopolysaccharides (LPS) (from Escherichia coli). Wistar rats were divided into five groups of 10 animals each. The control group received an intranasal saline solution once/day, for seven consecutive days. Rats in groups 2 and 3, received low-dose (5 μg) and high-dose (10 μg) of LPS, once/day, for seven consecutive days. Rats in groups 4 and 5, received low-dose (5 μg) and high-dose (10 μg) of LPS and after 2 h, 80 mg/kg of quercetin, once/day for seven consecutive days was administered. After the treatment period, the histopathological examination of nasal and sinus mucosa was performed and levels of cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)) and oxidative stress in the blood, nasal mucosa, lungs and brain were also analyzed. High dose of LPS increased TNF-α, IL-6 and IL-1β levels in serum, nasal mucosa, and lungs homogenates while in brain, this effect was only on TNF-α levels. IL-1β enhanced significantly in serum and mucosa, especially after administration of a high dose of LPS (P < 0.01 and P < 0.05). Histopathological and immunofluorescence analysis revealed acute inflammatory reaction in rats treated with both doses of LPS without significant changes of lipid peroxidation in the studied tissues. Quercetin administration diminished the exudate and degree of inflammation in lamina propria of nasal and sinusal areas, parallel with the decreased secretion of TNF-α (40.2% reduction after the low dose of LPS, and 35.4% reduction after the high dose of LPS) and IL-6 (21.4% reduction after the low dose of LPS and 35.8% reduction after the high dose of LPS). In lungs, quercetin reduced TNF-α (43.3%) and IL-6 levels (24.5%), and in the brain, the protective effect was noticed only on TNF-α (46.5%). The intranasal LPS administration successfully induced acute rhinosinusitis in a rat model and also generated an inflammatory response in the lungs and brain. Intranasal administration of quercetin diminished the nasal inflammation and also exerted protective effect on lungs and partially on brain inflammatory reaction.