In a statement, officials from the service said some 100 armed insurgents attacked the border guards' camp in Luhansk, a major eastern Ukrainian city not far from the Russian border, in the early hours.
Border guards responded with fire on the attackers whose numbers swelled to 400 a few hours later. The fighting was ongoing, the border guard service said.
Border guards lamented that neither the army nor the police has arrived with reinforcements yet.
Three months of protests during the winter drove pro-Russia president Viktor Yanukovych to flee the country. Many in Ukraine's east are suspicious of the new pro-Western government in Kiev.
Protesters in the east were rallying in early spring in favor of greater independence from the Ukrainian capital but that soon turned into a separatist movement as the Luhansk and the Donetsk regions declared independence following hastily called referenda.
The conflict between Ukrainian government forces and pro-Russian insurgents in eastern Ukraine escalated markedly in the last week, with rebels attempting to seize a major airport and the shooting down of a Ukrainian military helicopter.