In 1562, the province of Shirvan sent an envoy to Russia to establish official trade relations.Shamakhi subsequently did the same in 1653. The first Persians to engage in commercial trade with Russia were Armenians from Julfa, in northern Persia. Julfa was an important link in the Russo-Persian trade route originating in Gilan. In 1604, Shah Abbas I resettled a significant population of Armenians from Julfa to his newly established capital, Isfahan, giving them commercial rights. Shah Abbas extended credit, lowered taxes, and granted religious freedom to this Armenian population.

Russia annexed the Kazan and Astrakhan khanates in 1552 and 1556 respectively, to extend the Volga trade route to the Caucasus and the Caspian Sea. Significant points along this trade route were Gilan and Derbent, as the origins of the maritime and overland trade routes between Russia and Persia respectively, and the commercial centres of Astrakhan and Shamakhi. Shamakhi in particular was the site of much merchant trade from Russia: silks, leather, metal wares, furs, wax and tallow. Persian merchants traded in Russia, additionally, reaching as far as Nizhny Novgorod and Kazan, which developed into trade centres. In 1555, the Muscovy, or Russia Company was created for the sole purpose of overland trade with Persia.

In 1514, the Ottoman Empire instated a commercial blockade against Persia. In order to reduce this pressure from the Ottomans, Shah Abbas I attempted to establish alternate overland trade routes through Russia. An Ottoman attempt to capture Shirvan caused Shah Tahmasp I to send a diplomatic envoy to Moscow in 1552. In 1580, the Ottomans occupied Shirvan and parts of Khartli-Kakheti, including Tiflis. Ottoman forces also threatened Astrakhan, which was key to an important trade route and a Russian commercial centre. Shah Mohammed Khodabanda promised to cede Derbent and Baku to Russia following the liberation of these cities from the Ottoman Empire.

The earliest records of official relations between Russia and Persia show that in 1521, Shah Ismail I of the Safavid dynasty sent a diplomatic envoy to Tsar Vasili III of Muscovy. Commercial relations, however, were infrequent, and often involved Tatars acting as merchant intermediaries.

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