Palmyra changed hands on a number of occasions between different empires before becoming a subject of the Roman Empire in the first century AD.

The city grew wealthy from trade caravans; the Palmyrenes were renowned merchants who established colonies along the Silk Road and operated throughout the Roman Empire.

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Palmyra's senate was an example; although Palmyrene texts written in Greek described it as a "boule" (a Greek institution), the senate was a gathering of non-elected tribal elders (a Near-Eastern assembly tradition).

Palmyra provided the most convenient Eastern examples bolstering an art-history controversy at the turn of the 20th century: to what extent Eastern influence on Roman art replaced idealized classicism with frontal, hieratic and simplified figures (as believed by Josef Strzygowski and others).

According to the suggestion by Schultens, "Palmyra" could have arisen as a corruption of "Tadmor", via an unattested form "Talmura", changed to "Palmura" by influence of the Latin word palma (date "palm"), The second view, supported by some philologists, such as Jean Starcky, holds that Palmyra is a translation of "Tadmor" (assuming that it meant palm), which had derived from the Greek word for palm, "Palame".

An alternative suggestion connects the name to the Syriac tedmurtā (ܬܕܡܘܪܬܐ) "miracle", hence tedmurtā "object of wonder", from the root dmr "to wonder"; this possibility was mentioned favourably by Franz Altheim and Ruth Altheim-Stiehl (1973), but rejected by Jean Starcky (1960) and Michael Gawlikowski (1974).

In response to the destruction, on 21 October 2015, Creative Commons started the New Palmyra project, an online repository of three-dimensional models representing the city's monuments; the models were generated from images gathered, and released into the public domain, by the Syrian internet advocate Bassel Khartabil between 20.

Consultations with the UNESCO, UN specialized agencies, archaeological associations and museums produced plans to restore Palmyra; the work is postponed until the violence in Syria ends as many international partners fear for the safety of their teams as well as ensuring that the restored artifacts will not be damaged again by further battles.

During the Syrian Civil War in 2015, Palmyra came under the control of the Islamic State of Iraq and the Levant (ISIL), and subsequently changed hands several times between the militant group and the Syrian Army who retook the city on 2 March 2017.

ISIL sabotaged many artifacts and destroyed a number of buildings, considerably damaging the ancient site.

The city's inhabitants worshiped local Semitic deities, Mesopotamian and Arab gods.